Abstract 18192: Free Radical Scavenger Edaravone Inhibited Both Aneurysmal Formation and Progression in Rat Abdominal Aortic Aneurysm Model

Objective: Effective pharmaceutical treatment for abdominal aortic aneurysm (AAA) has not been established. Recent studies have reported that reactive oxygen species (ROS) are excessively expressed in the aneurysm wall. However, whether ROS play a crucial role in the aneurysm formation and its growth still remains unknown. We investigate ROS inhibition with the free radical scavenger edaravone effectively prevents aneurysm formation. Methods: Thirty male Sprague-Dawely rats were used to create experimental AAA model. Rats were divided into three groups; group C (control) received an intraperitoneal injection of saline at 30 minutes prior to the aneurysm preparation, group E (edaravone-early-treated) received an intraperitoneal injection of edaravone 5 mg/kg/day at 30 minutes prior to the aneurysm preparation, and the edaravone-late-treated group (group L) received the same dose of edaravone at 7 days after AAA preparation. At day 7, ROS production was semiquantified by dihydroethidium staining, and the oxidative product of DNA induced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), by immunohistochemical staining. The dilatation ratio of AAA at day 28 was calculated. Results: At day 7, dihydroethidium staining of aneurysm wall showed that ROS expression was significantly suppressed in group E compared with groups C and L (2.1±0.7 in group E, 4.3±1.8 in groups C and L, p=0.02). Positive cell count of 8-OHdG was significantly lower in group E than that in groups C and L. The aortic dilatation ratio (%) at day 28 in groups E was significantly lower than that in group C (36.7±2.0 vs. 104.7±16.0, p< 0.001) and in group L was significantly lower than that in group C (53.1±2.9 vs. 104.7±16.0, p< 0.001). Conslusion: ROS play a crucial role in the aneurysm formation. Edaravone treatment starting even at 7 days after aneurysm preparation completely inhibited aneurysmal growth. Edaravone could be effective pharmaceutical agent for AAA in clinical practice.